The goal of this research is to define the factors which influence thyroid hormone secretion, transport, cellular uptake and metabolism. Because of the recent evidence underlining the importance of triiodothyronine (T3) to the maintenance of the euthyroid state particular emphasis will be placed on quantitation of the relative importance of T3 and thyroxine (T4) in each of these areas. These aspects of thyroid physiology will be studied in euthyroid, hypothyroid and hyperthyroid man as well as in suitable animal models. Triiodothyronine levels will be measured using a sensitive immunoassay which can be performed directly on human serum and serum from other animal species. Thyroxine will be measured by immunoassay as well. Free T3 and T4 concentrations will be determined by ultrafiltration after enrichment with tracer T3 and T4. Thyroxine-binding protein-thyroid hormone interactions will be perturbed with the use of agents such as salicylates which have been shown by our previous studies to inhibit binding of T3 and T4 to thyroxine- binding globulin, thyroxine-binding prealbumin and albumin. Free hormone concentrations will be measured before and after introduction of these agents to determine whether there is a consistent dependent relationship between free hormone levels and T4 and T3 degradation. Kinetic analyses of the data will be performed by compartmental analysis. This study should enable us to quantitate the role of T3 and the maintenance of the euthyroid state and determine its importance in pathological thyroid conditions.